Alternative hormone therapies for prostate cancer examined

This review summarized recent evidence on alternatives to continuous androgen deprivation therapy (CADT). Authors reported that more high-quality evidence is needed to determine overall benefits of new hormonal treatment approaches compared to ADT.

Androgen deprivation therapy (ADT) is a type of hormone therapy that targets androgens, the male sex hormones (such as testosterone). Reducing androgen levels can dramatically improve survival among prostate cancer patients. ADT is currently the standard of care for metastatic prostate cancer (cancer that has spread to distant organs).

Many patients, however, can stop responding (become resistant) to ADT. In addition, ADT is associated with an increased risk of diabetes, brittle bones and potentially cardiovascular disease (heart and blood vessel disease). To decrease the risk of potential side effects, ADT can be applied intermittently (IADT), with breaks between treatments. Alternatively, newly developed treatments that target androgen receptors directly (also called androgen-receptor antagonists), are often recommended for men who no longer respond to, or do not tolerate, standard ADT. 

The focus of this review is to evaluate evidence on alternatives to standard ADT.

Two recent trials comparing CADT to IADT found no differences in overall survival (time from treatment until death from any cause). IADT was associated with some improvements in quality of life compared to CADT. Over the course of one study, more men receiving IADT died due to prostate cancer (41% of men) compared to CADT (34% of men). Death due to other causes (mainly cardiovascular disease) was more common in men receiving continuous ADT. However, another study reported higher rates of cardiovascular events (such as heart attack or stroke) over the course of 10 years with IADT (32% of men) than with CADT (23% of men).

Two separate trials have compared bicalutamide (Casodex), an androgen-receptor antagonist, to standard ADT. No difference in overall survival was noted between the two approaches. Men receiving bicalutamide had improved quality of life, including sexual interest and physical capacity. 

Enzalutamide (Xtandi) was the first androgen-receptor antagonist found to benefit overall survival in patients resistant to ADT. One trial found that 81% of patients responded in the first year and 67% in the second year of treatment. Among men with metastatic prostate cancer, 50% of men had a complete response (no sign of cancer) and 15% had a partial response (decrease in tumor size) to treatment with enzalutamide. Side effects, however, were comparable to those of standard ADT, including insulin resistance, weight gain, and high cholesterol levels, as well as breast tenderness. Enzalutamide did not increase the risk of brittle bones. 

The authors concluded that some alternative hormone therapies are as effective as ADT with fewer associated side effects. However, more high-quality evidence is needed to determine the overall benefits of alternative hormonal treatment approaches. Long-term safety of these treatments is still under investigation.